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Effects of Metreleptin in Type 1 Diabetes Mellitus

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01268644
Recruitment Status : Terminated (Sponsor request)
First Posted : December 31, 2010
Results First Posted : August 28, 2019
Last Update Posted : August 28, 2019
Juvenile Diabetes Research Foundation
Amylin Pharmaceuticals, LLC.
Information provided by (Responsible Party):
Abhimanyu Garg, University of Texas Southwestern Medical Center

Brief Summary:
This study will add leptin therapy to the current insulin therapy of Type 1 Diabetics with the aim of lowering the total insulin requirements and suppressing the steep fluctuations typically associated with Type 1 Diabetes.

Condition or disease Intervention/treatment Phase
Type 1 Diabetes Drug: Leptin Phase 1

Detailed Description:
The adipocyte hormone, leptin, has been shown to restore the health and glucoregulation of near-death, insulin deficient diabetic rodents. This makes leptin the only hormone, since the discovery of insulin in 1922, with this capability. Leptin normalizes the hyperglucagonemia of diabetes and reduces lipogenesis and cholesterologenenesis. Treatment of diabetic rodents with a combination of leptin and insulin, leads to a stable pattern of glucose control with reduced insulin requirements, as opposed to the high glucose variability that characterizes the treatment of type 1 diabetes with supraphysiologic doses of insulin alone. As such, we will initiate a pilot clinical trial to test combination leptin and insulin therapy in type 1 diabetes. Fifteen leptin sensitive patients (body mass index <27 kg/m²) with uncontrolled diabetes (HbA1c 7.0 to 10.0 %) will be treated with slightly supraphysiologic doses of recombinant human leptin (Amylin Pharmaceuticals). Subjects will be compared to themselves before and after treatment with leptin. Endpoint variables include HbA1c, change in daily insulin dose, mean and standard deviation of blood glucose from inpatient glucose monitoring and glucose meter download. We will also assess effects of leptin therapy on energy intake as assessed by 3-day food record and body weight and fat by DEXA. Intramyocellular and intrahepatic lipid concentration by 1H-MRS will be assessed before and after 3 months of metreleptin therapy. A satiety analysis will be employed. In addition, plasma hormones and inflammatory biomarkers will be assayed during the course of this study.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open Label Single Center Pilot Study to Study Teh Effects of Metreleptin Administration in Patients With Type 1 Diabetes Mellitus ( T1DM ).
Study Start Date : September 2010
Actual Primary Completion Date : January 2013
Actual Study Completion Date : August 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1
Drug Information available for: Metreleptin

Arm Intervention/treatment
Experimental: active open label Leptin
Active open label Leptin for type 1 Diabetes
Drug: Leptin
weight based sub-cutaneous injection twice daily of Leptin
Other Name: Metreleptin

Primary Outcome Measures :
  1. HbA1c [ Time Frame: Baseline and 12 weeks ]
    Change in Hba1c after 12 weeks on Leptin Therapy compared to Baseline value

Secondary Outcome Measures :
  1. Weight [ Time Frame: Baseline to 12 weeks ]
    Change in Body Weight after 12 weeks on Leptin Therapy compared to Baseline value

  2. Insulin Dose [ Time Frame: Baseline to 12 weeks ]
    Change in Insulin dose after 12 weeks on Leptin Therapy compared to Baseline value

  3. Change in HbA1c From Baseline to Week 20 on Leptin Therapy [ Time Frame: Baseline to Week 20 (On leptin) ]
    Change in Hba1c after 20 weeks on Leptin Therapy compared to Baseline value. With ongoing metreleptin therapy, the concomitant basal insulin dose was actively reduced by 50% after week 12.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

All of the following criteria are to be fulfilled for inclusion of an individual in the study. An eligible individual:

  1. Is male or female and is 18 to 50 years of age
  2. Has been diagnosed with T1DM for at least 1 year. Diagnosis of T1DM will be based on clinical criteria including: insulin-dependence within 6 months of the onset, history of prior episode of ketoacidosis, previous documentation of positive serum islet cell autoantibodies or low or undetectable serum C-peptide levels.
  3. Has an HbA1c 7.0 to 10.0 %, inclusive
  4. Currently on insulin pump or on a combination of basal (long-acting insulin preparation) and pre-prandial (short-acting insulin preparation) insulin therapy
  5. Is male, or if female of childbearing potential, is non-lactating, and has a negative pregnancy test (human chorionic gonadotropin, beta subunit [βhCG]) result at screening (Visit 1) and Visit 2 regardless of menopausal status (If female and of childbearing potential [including peri menopausal women who have had a menstrual period within one year], must practice and be willing to continue to practice appropriate birth control [defined as a method which results in a low failure rate, i.e., less than 1% per year, when used consistently and correctly, such as implants, injectables, oral contraceptives, some intrauterine contraceptive devices, sexual abstinence, tubal ligation, or a vasectomized partner] during the entire duration of the study.)
  6. Has a BMI < 27 kg/m2
  7. Has clinical laboratory test values (clinical chemistry, hematology, and urinalysis) judged to be not clinically significant by the investigator at screening (Visit 1)
  8. Has a physical examination and electrocardiogram (ECG) with no clinically significant abnormalities as judged by the investigator

Exclusion Criteria:

  1. Has a fasting serum triglyceride concentration >400 mg/dL at screening
  2. Has hypoglycemia unawareness (Loss of consciousness due to hypoglycemia without preceding symptoms or recent history of blood glucose <50 mg/dl without symptoms)
  3. Currently abuses drugs or alcohol, or has a history of abuse that in the investigator's opinion could cause the individual to be noncompliant with study procedures, or has a positive urine screen for drugs of abuse at screening (Visit 1)
  4. Has chronic renal insufficiency with serum creatinine > 2 mg/dL
  5. Has a history of weight loss (>3%) in the last 3 months
  6. Is currently enrolled or plans to enroll in a diet, weight loss, or exercise program
  7. Has a sitting blood pressure >160/95 mmHg (either systolic or diastolic) at screening (Visit 1)
  8. Has a clinically significant history or presence of any of the following conditions:

    • Active cardio- or cerebrovascular disease
    • Active pulmonary disease
    • Hepatic disease defined as follows:

      • At screening (Visit 1), alanine transaminase (ALT), aspartate transaminase (AST), or alkaline phosphatase > three times the upper limit of normal (elevated Liver Function Test values suggestive of obesity related non-alcoholic fatty liver disease may not be exclusionary)
    • The presence of any other co morbid disorders that, in the opinion of the investigator, would interfere with the subject's compliance of study procedures
    • Clinically significant malignancies within 5 years of screening (Visit 1)
    • Chronic infections (e.g., HIV [human immunodeficiency virus] or tuberculosis)
  9. Has received any investigational drug within 30 days or within a period corresponding to five half-lives of that drug, whichever is greater, before screening (Visit 1)
  10. Has had major surgery or a blood transfusion within 2 months before screening (Visit 1) or has a hematocrit < 30%
  11. Has a known hypersensitivity to any of the components of the study treatment (e.g. has a known hypersensitivity to E. Coli derived proteins
  12. Is an immediate family member (spouse, parent, child, or sibling; biological or legally adopted) of personnel directly affiliated with the study at the investigative site, or is personally directly affiliated with the study at the investigative site
  13. Is employed by Amylin Pharmaceuticals, Inc., (i.e., an employee, temporary contract worker, or designee responsible for the conduct of the study)
  14. Has previously received treatment with recombinant leptin (metreleptin or Fc leptin)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01268644

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United States, Texas
UT Southwestern Medical Center
Dallas, Texas, United States, 75390
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Juvenile Diabetes Research Foundation
Amylin Pharmaceuticals, LLC.
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Principal Investigator: Abhimanyu Garg, M.D. UT Southwestern Medical Center
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Responsible Party: Abhimanyu Garg, Chief, Division Nutrition and Metabolic Diseases, Professor Internal Medicine, University of Texas Southwestern Medical Center Identifier: NCT01268644    
Other Study ID Numbers: FBA937
CTRC # 953 ( Other Grant/Funding Number: JDRF and Amylin )
First Posted: December 31, 2010    Key Record Dates
Results First Posted: August 28, 2019
Last Update Posted: August 28, 2019
Last Verified: July 2019
Keywords provided by Abhimanyu Garg, University of Texas Southwestern Medical Center:
Type 1 Diabetes Mellitus
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases